공시 • Jun 27
Actinogen Medical Limited Announces the Peer-Reviewed Publication of its Phase 2a Biomarker
Actinogen Medical Limited announced the peer-reviewed publication of its phase 2a biomarker trial entitled "Plasma pTau181 Predicts Clinical Progression In A Phase 2 Randomized Controlled Trial of the 11ß-HSD1 Inhibitor Xanamem for Mild Alzheimer's Disease" in the 100th edition of the Journal of Alzheimer's Disease. Highlights of the publication include: Participants comprised 72 patients from the previous XanADu phase 2a trial of mild Alzheimer's disease (AD) who had available stored plasma (blood) samples and gave informed consent for the new trial Patients with elevated pTau181 had much more rapid progression than patients with lower levels in four key clinical endpoints: ADCOMS (p<0.001), CDR-SB (p<0.001), MMSE (p=0.12) and ADAS-Cog14 (p=0.19). In the 34 patients with elevated pTau181 a potentially large and clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS[2] mean difference 0.6 units, p=0.09) and positive trends were observed in a Neuropsychological Test Battery of cognition (LS mean difference 1.8 units, p=NS). The biomarker trial was conducted as a stand-alone, prospective, double-blind trial using newly generated plasma biomarker data and clinical data on file from the XanADu phase 2a trial in patients with a clinical diagnosis of mild AD. The protocol and statistical analysis plan were pre-defined and data were analyzed in a blinded manner. No trial or laboratory personnel knew the treatment assignment of the participants until the final analysis results were generated. The 72 participants in the trial had been treated with Xanamem 10mg or placebo once daily for 12 weeks. The panel of biomarkers was analyzed by a leading laboratory in Sweden, the Clinical Neurochemistry Laboratory, University of Gothenburg, who were "blinded" to treatment assignment, and included pTau181, amyloid beta1-40 and -42, glial fibrillary acidic protein, and neurofilament light. The placebo group had 34 participants with analyzable plasma pTau181 levels. Those with elevated pTau181 (n=18) showed more rapid clinical progression than patients with lower levels (n=16) in four key clinical endpoints: ADCOMS (d=0.55, p<0.001), CDR-SB (d=0.63, p<0.001), MMSE (d=0.52, p=0.12) and ADAS-Cog14 (d=0.53, p=0.19). The Cohen's d statistics (the effect of high/low pTau181 as a proportion of the baseline standard deviation) were quite large and participants with low pTau generally did not worsen during the 12 week trial. This confirms that the original XanADu trial population contained a high proportion of non-progressive patients, many of whom may have had an alternative diagnosis to AD (there was no routine use of biomarker or imaging confirmation of the diagnosis of AD at the time the trial was designed). The results from this trial are consistent with emerging data from other trials and recently updated international guidelines that consider elevated plasma pTau as a viable diagnostic option for AD. The company believes plasma pTau is particularly useful as an alternative or adjunct to amyloid PET brain scans for the selection of patients with progressive disease in AD trials. The on-going XanaMIA phase 2b Alzheimer's disease trial is using elevated plasma pTau181 levels to select patients in whom a Xanamem treatment effect is more likely to be demonstrable over the 36-week treatment period. The primary evaluation of the efficacy of Xanamem was conducted in the high pTau181 group (n=34) who were considered to have biomarker-confirmed AD. A large and potentially clinically meaningful Xanamem treatment effect compared to placebo was seen in the CDR-SB (LS mean difference 0.6 units, d=0.41, p=0.09). Positive trends were also seen in a Neuropsychological Test Battery of cognition (LS mean difference 1.8 units, d=0.26, p=NS) but not for other endpoints. These results suggest that the potential cognitive enhancement and disease-slowing benefits of Xanamem may be sensitively detected with the CDR-SB endpoint, which is an 18-point score that rates both functional and cognitive abilities. Using the cognitive findings from this trial and prior trials showing benefit on attention and working memory, a cognitive composite has been designed for use in future Xanamem trials. This cognitive composite and the CDR-SB are key endpoints in the on-going XanaMIA phase 2b trial in participants with mild to moderate AD whose diagnosis will be confirmed by elevated pTau181 levels. The XanaMIA trial is anticipated to report interim results mid-2025 and final results in 2026. The XanaCIDD Phase 2a cognition & depression trial is a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 167 patients. Participants are evenly randomized to receive Xanamem 10 mg once daily or placebo, in some cases in addition to their existing antidepressant therapy, and effects on cognition and depression are assessed. Results are due to be reported early in Third Quarter 2024. The XanaMIA Phase 2b Alzheimer's disease trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in 220 patients with mild to moderate AD and progressive disease, determined by clinical criteria and confirmed by an elevated level of the pTau181 protein biomarker in blood. Patients receive Xanamem 10 mg or placebo, once daily, and effects on cognition, function and progression of Alzheimer's disease are assessed. Thus, Xanamem is being assessed in this trial for its potential effects as a both a cognitive enhancer and a disease course modifier. Interim results are due to be reported in mid-2025, with final results in 2026.
